土木香提取物对金黄色葡萄球菌分选酶A抑制作用
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摘要
金黄色葡萄球菌耐药性较为严重,细菌性分选酶A在细菌细胞壁表面毒力蛋白锚定过程中发挥着重要作用,是细菌性感染防治的重要潜在靶点。研究通过酶活抑制试验、细胞外基质黏附试验、生物被膜形成试验和细菌侵袭试验进行了分选酶A抑制剂筛选和活性分析。结果表明:土木香提取物可显著抑制金葡菌分选酶A活性,土木香提取物处理后可显著降低金葡菌与细胞外基质黏附及金葡菌生物被膜形成。在金葡菌与宿主细胞共感染体系内加入土木香提取物后可显著降低细菌对宿主细胞的侵袭作用。说明土木香提取物可通过靶向分选酶从而抑制金葡菌的致病力,是潜在的抗金葡菌感染先导复合物。
Bacterial resistance has become one of the most urgent global problems in this century,in which drug-resistant Staphylococcus aureus has attracted much attention. Sortase A is indispensable for the anchorage of virulence associated surface proteins,suggesting that this protein is an ideal target for developing anti-infective drugs. Sortase A activity inhibition assay,extracellular matrix adhesion assay,bacterial biofilm formation assay and bacterial invasive assay were performed to indentify sortase A inhibitor and its inhibitory effect against S. aureus virulence. We found that Inulae Radix extracts could significantly inhibit the activity of sortase A. Furthermore,treatment with Inulae Radix extracts significantly reduced the adhesion of S. aureus to extracellular matrix and the formation of bacterial biofilm. Additionally,the addition of Inulae Radix extracts into the co-culture system of S. aureus and host cells could significantly inhibit the invasion of bacteria to host cells. Our results indicated that Inulae Radix extracts could attenuate S. aureus virulence by targeting sortase A,suggesting that Inulae Radix extracts may represent a leading compound for S. aureus infection.
Bacterial resistance has become one of the most urgent global problems in this century,in which drug-resistant Staphylococcus aureus has attracted much attention. Sortase A is indispensable for the anchorage of virulence associated surface proteins,suggesting that this protein is an ideal target for developing anti-infective drugs. Sortase A activity inhibition assay,extracellular matrix adhesion assay,bacterial biofilm formation assay and bacterial invasive assay were performed to indentify sortase A inhibitor and its inhibitory effect against S. aureus virulence. We found that Inulae Radix extracts could significantly inhibit the activity of sortase A. Furthermore,treatment with Inulae Radix extracts significantly reduced the adhesion of S. aureus to extracellular matrix and the formation of bacterial biofilm. Additionally,the addition of Inulae Radix extracts into the co-culture system of S. aureus and host cells could significantly inhibit the invasion of bacteria to host cells. Our results indicated that Inulae Radix extracts could attenuate S. aureus virulence by targeting sortase A,suggesting that Inulae Radix extracts may represent a leading compound for S. aureus infection.
引文
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[8]陈博,张安定,许仲旻,等.高通量鉴定病原菌表面蛋白与宿主细胞表面分子之间的相互作用[C]∥中国畜牧兽医学会动物传染病学分会.中国畜牧兽医学会动物传染病学分会第十二次人兽共患病学术研讨会暨第六届第十四次教学专业委员会论文集,长春:[s.n.],2012:8.
[9]Spirig T,Weiner E M,Clubb R T.Sortase enzymes in Grampositive bacteria[J].Mol Microbiol,2011,82(5):1044-1059.
[10]Chen F,Liu B,Wang D,et al.Role of sortase A in the pathogenesis of Staphylococcus aureus-induced mastitis in mice[J].FEMS Microbiology Letters,2014,351(1):95-103.
[11]Cegelski L,Marshall G R,Eldridge G R,et al.The biology and future prospects of antivirulence therapies[J].Nature Reviews Microbiology,2008,6(1):17-27.
[12]Rasko D A,Sperandio V.Anti-virulence strategies to combat bacteria-mediated disease[J].Nature Reviews Drug Discovery,2010,9(2):117-128.
[13]毕重伟,王琳,王大成,等.咖啡酸通过抑制分选酶A治疗金黄色葡萄球菌感染小鼠[J].吉林农业大学学报,2016,38(3):336-340.
[2]Maresso A W,Schneewind O.Sortase as a target of anti-infective therapy[J].Pharmacol Rev,2008,60(1):128-141.
[3]Cossart P,Jonquieres R.Sortase,a universal target for therapeutic agents against Gram-positive bacteria?[J].P Natl Acad Sci,2000,97(10):5013-5015.
[4]Cascioferro S,Totsika M,Schillaci D.Sortase A:An ideal target for anti-virulence drug development[J].Microb Pathogenesis,2014,77:105-112.
[5]Wang L,Bi C W,Cai H J,et al.The therapeutic effect of chlorogenic acid against Staphylococcus aureus infection through sortase A inhibition[J].Front Microbiol,2015,6:1031.
[6]张乐,方羽,陆国红.土木香化学成分及药理研究概况[J].中成药,2015,37(6):1313-1316.
[7]迟戈夫.异鼠李素抗金黄色葡萄球菌α溶血素和分选酶A作用研究[D].长春:吉林大学,2016.
[8]陈博,张安定,许仲旻,等.高通量鉴定病原菌表面蛋白与宿主细胞表面分子之间的相互作用[C]∥中国畜牧兽医学会动物传染病学分会.中国畜牧兽医学会动物传染病学分会第十二次人兽共患病学术研讨会暨第六届第十四次教学专业委员会论文集,长春:[s.n.],2012:8.
[9]Spirig T,Weiner E M,Clubb R T.Sortase enzymes in Grampositive bacteria[J].Mol Microbiol,2011,82(5):1044-1059.
[10]Chen F,Liu B,Wang D,et al.Role of sortase A in the pathogenesis of Staphylococcus aureus-induced mastitis in mice[J].FEMS Microbiology Letters,2014,351(1):95-103.
[11]Cegelski L,Marshall G R,Eldridge G R,et al.The biology and future prospects of antivirulence therapies[J].Nature Reviews Microbiology,2008,6(1):17-27.
[12]Rasko D A,Sperandio V.Anti-virulence strategies to combat bacteria-mediated disease[J].Nature Reviews Drug Discovery,2010,9(2):117-128.
[13]毕重伟,王琳,王大成,等.咖啡酸通过抑制分选酶A治疗金黄色葡萄球菌感染小鼠[J].吉林农业大学学报,2016,38(3):336-340.